zn2+和金属硫蛋白在细胞内表达的关系.pptVIP

（资料来源： Saydam等，2001） 图45：PKC抑制剂对老鼠肾脏细胞中MTF-1磷 酸化水平的影响 图44：PKC抑制剂对老鼠肾脏细胞中MTF-1磷酸化水平的影响 （资料来源：Adams等，2002） 说明：Zn2+激活的MT基因的转录可能是受到去磷酸化的MTF-1的调节。可能原因是，Zn2+诱导磷酸化的MTF-1进入细胞核，而特异的残基去磷酸化，最后激活MT基因的转录。 六﹑结语 1.外源性添加Zn2+能够诱导细胞内MT的表达。 2.外源性诱导剂NO，H2O2以及重金属离子诱导MT在细 胞内的表达依赖于MT中Zn2+的作用。 3.Zn2+诱导MT在细胞内的表达分为三个过程： 第一，Zn2+与MTF-1的锌指结合；第二，Zn2+通过PKC等 几种酶诱导MTF-1的磷酸化；第三，Zn2+介导活性的 MTF-1进入细胞核，最后活性的MTF-1与MRE结合，启动 MT的转录发生。 七，参考文献 Aravindakumar,C.T.,Ceulemans,J.,De Ley,M.,1999.Nitric oxide induces Zn2+ release from metallothionein by destroying zinc-sulphur clusters without concomitant formation of S-nitrosothiol.Biochem.J.344,253-258. Berendji,D.,KolbBachofen,V.,Meyer,K.L.,Grapenthin,O.,Weber,H.,Wahn,V.,Kroncke,K.D.,1997.Nitric oxide mediates intracytoplasmic and intranuclear zinc release.FEBS Lett.405,37–41. Bittel,D.,Dalton,T.,Samson,S.L.-A.,Gedamu,L.,Andrews,G.K.,1998.The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc,but not by other transition metals.J.Biol.Chem.273,7127–7133. Chen,X.,M.Chu,and D.P.Giedroc.1999.MRE-binding transcription factor-1:weak zinc-binding finger domains 5 and 6 modulate the structure, affinity,and specificity of the metal-response element complex.Biochemistry 38:12915–12925. Dalton,T.P.,Li,Q.,Bittel,D.,Liang,L.,Andrews,G.K.,1996.Oxidative stress activates metal-responsive transcription factor-1 binding activity.J.Biol.Chem.271,26233–26241. Dalton,T.P.,Bittel,D.,Andrews,G.K.,1997.Reversible activation of mouse metal response element-binding transcription factor 1 DNA binding involves zinc interaction with the zinc finger domain.Mol.Cell.Biol.17,2781–2789. Giedroc,D.P.,Chen,X.,Apuy,J.L.,2001.Metal response element(MRE)-binding transcription factor-1(MTF-1):structure,function,and regulation.Antioxid.Redox Signal.3(4),577–596. Heuchel,R.,Radtke,F.,Georgiev,O.,Stark,G.,Aguet,M.,Schaffner,W.,1994.The transcription factor MTF-1 is essential for basal and heavy meta